Project Background: Traumatic brain injury (TBI) is estimated to have occurred in 10 to 23% of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combatants, resulting in cognitive, neurobehavioral, and emotional sequelae and disability. Diagnosis in the chronic phase is difficult because conventional brain imaging is insensitive, acute injury records may be unavailable, and symptoms of posttraumatic stress disorder (PTSD) often overlap with those of TBI. Advanced brain imaging of TBI could potentially identify disruption of white matter (WM) tracts on diffusion tensor imaging (DTI), alterations in brain activation while performing cognitive tasks during functional magnetic resonance imaging (fMRI), and changes in functional connectivity (FC) measured from resting state fMRI. Rationale: We reported that TBI indexed by DTI was related to increases in brain activation in Veterans while they performed a spatial conflict resolution (SPCR) task, a finding that we and others have attributed to increased demand upon neural resources due to WM injury. PTSD symptom severity had the opposite effect of reducing task-related brain activation. Limitations of this study included restriction to blast TBI, lack of a definitive diagnostic instrument for PTSD, and the possibility that our findings were specific to the SPCR task. We also did not evaluate resting state FC. Objectives: Study blast and non-blast mechanisms of mild TBI (mTBI), add an fMRI task of complex attention that is likely to be more sensitive to diffuse WM injury, measure FC of the default mode network (DMN), explore the effects of blast exposure in Veterans without a history of mTBI, and perform a comprehensive analysis to examine multi-modality brain imaging in relation to outcome measures. This project will determine relationships between WM tract injury (DTI), fMRI brain activation during SPCR and attention tasks, connectivity during resting state fMRI, and functional, emotional, and cognitive status in mTBI and non-TBI groups. Methods: Study SPCR and complex attention-related brain activation in 60 mTBI (e 3 months post-injury) and 60 non-TBI without blast exposure, as well as 20 Veterans and Service Members with a history of blast exposure but not TBI. DTI will measure WM integrity and resting state fMRI will provide a measure of FC. We will assess cognitive, emotional, and functional outcome to address the Aims and the Clinician Assisted PTSD Scale will be used to identify subjects with PTSD. Statistical analyses will integrate the multimodality brain imaging to evaluate the contributions of mTBI and PTSD to brain activation on the SPCR and attention tasks, as well as FC. The array of brain imaging variables will be analyzed in relation to cognitive, emotional, and functional outcome. Relevance to Veterans' Healthcare: Improved diagnosis of chronic mTBI, including effects of blast exposure without a history of TBI, would facilitate treatment planning and lead to earlier referral. Information about mechanisms may also suggest intervention approaches for TBI and PTSD and provide methods for assessing treatment response.